Etiology and pathogenesis of periodontal diseases.

The two most prevalent and most investigated periodontal diseases are dental plaque-induced gingivitis and chronic periodontitis. The last 10 to 15 years have seen the emergence of several important new findings and concepts regarding the etiopathogenesis of periodontal diseases. These findings include the recognition of dental bacterial plaque as a biofilm, identification and characterization of genetic defects that predispose individuals to periodontitis, host-defense mechanisms implicated in periodontal tissue destruction, and the interaction of risk factors with host defenses and bacterial plaque. This article reviews current aspects of the etiology and pathogenesis of periodontal diseases.

[1]  R. Schultz,et al.  Comparison of NK-cell (Leu-7+ and Leu-11b+) populations in clinically healthy gingiva, chronic gingivitis and chronic adult periodontitis. , 1989, Journal of periodontal research.

[2]  S. Socransky,et al.  Effect of systemic matrix metalloproteinase inhibition on periodontal wound repair: a proof of concept trial. , 2004, Journal of periodontology.

[3]  A. C. Johannessen,et al.  Variational expression of functionally different macrophage markers (27E10, 25F9, RM3/1) in normal gingiva and inflammatory periodontal disease. , 1995, Journal of clinical periodontology.

[4]  L. Kesavalu,et al.  Porphyromonas gingivalis virulence in mice: induction of immunity to bacterial components , 1992, Infection and immunity.

[5]  C. Overall,et al.  Identification of polymorphonuclear leukocyte collagenase and gelatinase activities in mouthrinse samples: correlation with periodontal disease activity in adult and juvenile periodontitis. , 1990, Journal of periodontal research.

[6]  G. Seymour,et al.  Phenotypic and functional analysis of T cells extracted from chronically inflamed human periodontal tissues. , 1987, Journal of periodontology.

[7]  R. Arnold,et al.  Monocytic TNF alpha secretion patterns in IDDM patients with periodontal diseases. , 1997, Journal of clinical periodontology.

[8]  R. Genco,et al.  A role for fimbriae in Porphyromonas gingivalis invasion of oral epithelial cells , 1997, Infection and immunity.

[9]  M. Arvanitidou,et al.  Effect of periodontal therapy on crevicular fluid interleukin-1beta and interleukin-10 levels in chronic periodontitis. , 2004, Journal of dentistry.

[10]  M. Netea,et al.  Does the shape of lipid A determine the interaction of LPS with Toll-like receptors? , 2002, Trends in immunology.

[11]  P. Kolenbrander,et al.  Oral microbial communities: biofilms, interactions, and genetic systems. , 2000, Annual review of microbiology.

[12]  Yung-Hua Li,et al.  A Quorum-Sensing Signaling System Essential for Genetic Competence in Streptococcus mutans Is Involved in Biofilm Formation , 2002, Journal of bacteriology.

[13]  G. Roberts,et al.  Prevalence of Periodontal Pathogens in Dental Plaque of Children , 2004, Journal of Clinical Microbiology.

[14]  D. Graves,et al.  IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. , 1998, Journal of immunology.

[15]  H. Löe,et al.  Experimental gingivitis in man. II. A longitudinal clinical and bacteriological investigation. , 1966, Journal of periodontal research.

[16]  R. Genco,et al.  Serum Cotinine Levels, Smoking, and Periodontal Attachment Loss , 1996, Journal of dental research.

[17]  A. V. van Winkelhoff,et al.  Peptostreptococcus micros smooth and rough genotypes in periodontitis and gingivitis. , 2000, Journal of periodontology.

[18]  Hideo Mitani,et al.  Periodontal Ligament Cells Under Mechanical Stress Induce Osteoclastogenesis by Receptor Activator of Nuclear Factor κB Ligand Up‐Regulation via Prostaglandin E2 Synthesis , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[19]  R. Genco,et al.  Effects of smoking and smoking cessation on healing after mechanical periodontal therapy. , 1997, Journal of the American Dental Association.

[20]  M. Listgarten,et al.  3-year longitudinal study of the periodontal status of an adult population with gingivitis. , 1985, Journal of clinical periodontology.

[21]  M. Srivastava,et al.  Failure of macrophage activation in destructive periodontal disease , 1998, The Journal of pathology.

[22]  R. Seymour,et al.  Flurbiprofen in the prevention and treatment of experimental gingivitis. , 1993, Journal of clinical periodontology.

[23]  H. Jenkinson,et al.  Streptococcal adhesion and colonization. , 1997, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[24]  F E Dewhirst,et al.  Diversity of cultivable and uncultivable oral spirochetes from a patient with severe destructive periodontitis , 1994, Infection and immunity.

[25]  P. Marsh,et al.  Use of continuous flow techniques in modeling dental plaque biofilms. , 1999, Methods in enzymology.

[26]  D. Grenier,et al.  Oral microbial heat-shock proteins and their potential contributions to infections. , 2003, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[27]  C. Serhan,et al.  Resolution of Inflammation: A New Paradigm for the Pathogenesis of Periodontal Diseases , 2003, Journal of dental research.

[28]  S. Socransky,et al.  The predominant cultivable microbiota of crevicular epithelial cells. , 1989, Oral microbiology and immunology.

[29]  Yung-Hua Li,et al.  Novel Two-Component Regulatory System Involved in Biofilm Formation and Acid Resistance in Streptococcus mutans , 2002, Journal of bacteriology.

[30]  A. Tanner,et al.  Campylobacter Species in Health, Gingivitis, and Periodontitis , 2000, Journal of dental research.

[31]  T. H. Howell,et al.  Altering the progression of human alveolar bone loss with the non-steroidal anti-inflammatory drug flurbiprofen. , 1989, Journal of periodontology.

[32]  D. Rennick,et al.  Accelerated Alveolar Bone Loss in Mice Lacking Interleukin-10 , 2003, Journal of dental research.

[33]  H. Loe,et al.  ABSENCE AND PRESENCE OF FLUID FROM NORMAL AND INFLAMED GINGIVAE. , 1965, Periodontics.

[34]  D. Graves,et al.  Interleukin-1 and tumor necrosis factor antagonists inhibit the progression of inflammatory cell infiltration toward alveolar bone in experimental periodontitis. , 1998, Journal of periodontology.

[35]  H. Löe,et al.  Experimental periodontitis in the beagle dog. , 1973, Journal of periodontal research.

[36]  S. Socransky,et al.  Patterns of progression and regression of advanced destructive periodontal disease. , 1982, Journal of clinical periodontology.

[37]  K. Kornman,et al.  Clinical and microbiological evaluation of therapy for juvenile periodontitis. , 1985, Journal of periodontology.

[38]  P. Bork,et al.  Identification and mutation analysis of the complete gene for Chediak–Higashi syndrome , 1996, Nature Genetics.

[39]  E. Lally,et al.  Evidence for the role of highly leukotoxic Actinobacillus actinomycetemcomitans in the pathogenesis of localized juvenile and other forms of early-onset periodontitis. , 2000, Journal of periodontology.

[40]  T. Hart,et al.  Genetic factors in the pathogenesis of periodontitis. , 1997, Periodontology 2000.

[41]  Whasun O. Chung,et al.  Signaling System in Porphyromonas gingivalis Based on a LuxS Protein , 2001, Journal of bacteriology.

[42]  M. Engelgau,et al.  The Evolving Diabetes Burden in the United States , 2004, Annals of Internal Medicine.

[43]  A. Togari,et al.  Differential Expression of RANKL and Osteoprotegerin in Gingival Crevicular Fluid of Patients with Periodontitis , 2004, Journal of dental research.

[44]  Y. Konttinen,et al.  Activation of latent human neutrophil collagenase by reactive oxygen species and serine proteases. , 1990, Biochemical and biophysical research communications.

[45]  N. Lang,et al.  Microbial changes associated with the development of puberty gingivitis. , 1990, Journal of periodontal research.

[46]  T. Kislinger,et al.  Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice. , 2000, The Journal of clinical investigation.

[47]  B. Spratt,et al.  Penicillin-resistant viridans streptococci have obtained altered penicillin-binding protein genes from penicillin-resistant strains of Streptococcus pneumoniae. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[48]  S. Deguchi,et al.  Neutrophil-mediated damage to human periodontal ligament-derived fibroblasts: role of lipopolysaccharide. , 1990, Journal of periodontal research.

[49]  L. Kesavalu,et al.  Porphyromonas gingivalis virulence in a murine lesion model: effects of immune alterations. , 1997, Microbial pathogenesis.

[50]  P. Marsh,et al.  The effect of growth rate and haemin on the virulence and proteolytic activity of Porphyromonas gingivalis W50. , 1994, Microbiology.

[51]  R. Page Milestones in periodontal research and the remaining critical issues. , 1999, Journal of periodontal research.

[52]  S. Alaluusua,et al.  Periodontal findings in Cohen syndrome with chronic neutropenia. , 1997, Journal of periodontology.

[53]  H. Ohta,et al.  The relationships between leukotoxin production, growth rate and the bicarbonate concentration in a toxin-production-variable strain of Actinobacillus actinomycetemcomitans. , 1996, Microbiology.

[54]  M. A. Curtis,et al.  Molecular genetics and nomenclature of proteases of Porphyromonas gingivalis. , 1999, Journal of periodontal research.

[55]  V. Uitto,et al.  Localization of heat shock proteins in clinical Actinobacillus actinomycetemcomitans strains and their effects on epithelial cell proliferation. , 2000, FEMS microbiology letters.

[56]  J. Costerton Overview of microbial biofilms , 1995, Journal of Industrial Microbiology.

[57]  J C Gunsolley,et al.  Evidence of a substantial genetic basis for risk of adult periodontitis. , 2000, Journal of periodontology.

[58]  S. Wolff,et al.  The Chediak-Higashi syndrome: studies in four patients and a review of the literature. , 1972, Medicine.

[59]  J. Slots,et al.  Longitudinal study of experimentally induced periodontal disease in Macaca arctoides: relationship between microflora and alveolar bone loss , 1979, Infection and immunity.

[60]  G. Embery,et al.  Reactive oxygen species: a potential role in the pathogenesis of periodontal diseases. , 2008, Oral diseases.

[61]  W. Loesche,et al.  The subgingival microbial flora during pregnancy. , 1980, Journal of periodontal research.

[62]  Gillig Jl,et al.  The Chediak-Higashi syndrome: case report. , 1970 .

[63]  W. Loesche,et al.  Periodontal Disease as a Specific, albeit Chronic, Infection: Diagnosis and Treatment , 2001, Clinical Microbiology Reviews.

[64]  J. Ebersole,et al.  Phenotypic analyses of mononuclear cells recovered from healthy and diseased human periodontal tissues , 1987, Journal of Clinical Immunology.

[65]  C Bos,et al.  Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. , 2000, Blood.

[66]  R. Genco,et al.  Serology of oral Actinobacillus actinomycetemcomitans and serotype distribution in human periodontal disease , 1983, Infection and immunity.

[67]  P. Kolenbrander,et al.  Identification of Saliva-Regulated Genes of Streptococcus gordonii DL1 by Differential Display Using Random Arbitrarily Primed PCR , 2000, Infection and Immunity.

[68]  A. Holmlund,et al.  Bone resorbing activity and cytokine levels in gingival crevicular fluid before and after treatment of periodontal disease. , 2004, Journal of clinical periodontology.

[69]  M. Timmerman,et al.  Effect of pre-experimental maintenance care duration on the development of gingivitis in a partial mouth experimental gingivitis model. , 1994, Journal of periodontal research.

[70]  Robert J. Palmer,et al.  Communication among Oral Bacteria , 2002, Microbiology and Molecular Biology Reviews.

[71]  C. Clish,et al.  Reduced Inflammation and Tissue Damage in Transgenic Rabbits Overexpressing 15-Lipoxygenase and Endogenous Anti-inflammatory Lipid Mediators 1 , 2003, The Journal of Immunology.

[72]  C. Morton,et al.  LFA-1 immunodeficiency disease. Definition of the genetic defect and chromosomal mapping of alpha and beta subunits of the lymphocyte function-associated antigen 1 (LFA-1) by complementation in hybrid cells , 1986, The Journal of experimental medicine.

[73]  M. Nunn,et al.  Prognosis versus actual outcome. IV. The effectiveness of clinical parameters and IL-1 genotype in accurately predicting prognoses and tooth survival. , 1999, Journal of periodontology.

[74]  H. Rylander,et al.  Manifestations and treatment of periodontal disease in a patient suffering from cyclic neutropenia. , 1981, Journal of clinical periodontology.

[75]  H. Fletcher,et al.  Protease-active extracellular protein preparations from Porphyromonas gingivalis W83 induce N-cadherin proteolysis, loss of cell adhesion, and apoptosis in human epithelial cells. , 2001, Journal of periodontology.

[76]  H. Löe,et al.  Natural history of periodontal disease in man. Rapid, moderate and no loss of attachment in Sri Lankan laborers 14 to 46 years of age. , 1986, Journal of clinical periodontology.

[77]  D. Relman,et al.  Bacterial diversity within the human subgingival crevice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[78]  Paul Zimmet,et al.  Type 2 diabetes in the young: the evolving epidemic: the international diabetes federation consensus workshop. , 2004, Diabetes care.

[79]  G. Greenstein,et al.  A critical assessment of interleukin-1 (IL-1) genotyping when used in a genetic susceptibility test for severe chronic periodontitis. , 2002, Journal of periodontology.

[80]  B. Michalowicz,et al.  Human herpesviruses and Porphyromonas gingivalis are associated with juvenile periodontitis. , 2000, Journal of periodontology.

[81]  A. Klinger,et al.  The relationship between periodontal diseases and diabetes: an overview. , 2001, Annals of periodontology.

[82]  R. Kent,et al.  The interleukin-10 knockout mouse is highly susceptible to Porphyromonas gingivalis-induced alveolar bone loss. , 2004, Journal of periodontal research.

[83]  T. Lundgren,et al.  Impaired Cytotoxicity in Papillon-Lefèvre Syndrome , 2005, Journal of dental research.

[84]  S. Socransky,et al.  Gram negative species associated with active destructive periodontal lesions. , 1985, Journal of clinical periodontology.

[85]  D. Oda,et al.  Neutrophil-mediated damage to human gingival epithelial cells. , 1992, Journal of periodontal research.

[86]  A. Mombelli,et al.  Effect of smoking on gingival crevicular fluid cytokine profile during experimental gingivitis. , 2003, Journal of clinical periodontology.

[87]  R. Reinhardt,et al.  In situ lymphocyte subpopulations from active versus stable periodontal sites. , 1988, Journal of periodontology.

[88]  U. Göbel,et al.  Treponema putidum sp. nov., a medium-sized proteolytic spirochaete isolated from lesions of human periodontitis and acute necrotizing ulcerative gingivitis. , 2004, International journal of systematic and evolutionary microbiology.

[89]  S. Hamada,et al.  Relationship of periodontopathic bacteria with early-onset periodontitis in Down's syndrome. , 2001, Journal of periodontology.

[90]  R. Burne,et al.  Regulation of the gtfBC and ftf genes of Streptococcus mutans in biofilms in response to pH and carbohydrate. , 2001, Microbiology.

[91]  C. Scapoli,et al.  Modulation of clinical expression of plaque-induced gingivitis. II. Identification of "high-responder" and "low-responder" subjects. , 2004, Journal of clinical periodontology.

[92]  S. Socransky,et al.  The Bacterial Etiology of Destructive Periodontal Disease: Current Concepts. , 1992, Journal of periodontology.

[93]  J. Orange Human natural killer cell deficiencies and susceptibility to infection. , 2002, Microbes and infection.

[94]  R. Crout,et al.  Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis. , 2000, Journal of periodontology.

[95]  J. Zambon Actinobacillus actinomycetemcomitans in human periodontal disease. , 1985, Journal of clinical periodontology.

[96]  M. Levine,et al.  Characterization of in vivo salivary-derived enamel pellicle. , 1989, Archives of oral biology.

[97]  S. Socransky,et al.  Clinical, microbiological and immunological features of subjects with destructive periodontal diseases. , 1988, Journal of clinical periodontology.

[98]  D. Graves,et al.  Inflammation and tissue loss caused by periodontal pathogens is reduced by interleukin-1 antagonists. , 2002, The Journal of infectious diseases.

[99]  J. Clayton-Smith,et al.  Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport. , 2003, American journal of human genetics.

[100]  S. Socransky,et al.  The predominant cultivable microbiota of active and inactive lesions of destructive periodontal diseases. , 1988, Journal of clinical periodontology.

[101]  J. Gunsolley,et al.  Smoking and its effects on early-onset periodontitis. , 1995, Journal of the American Dental Association.

[102]  J. Lambeth,et al.  Altered diacylglycerol level and metabolism in neutrophils from patients with localized juvenile periodontitis , 1992, Infection and immunity.

[103]  B. Beilin,et al.  Immune response in asymptomatic smokers , 2002, Acta anaesthesiologica Scandinavica.

[104]  J. Costerton,et al.  Testing the susceptibility of bacteria in biofilms to antibacterial agents , 1990, Antimicrobial Agents and Chemotherapy.

[105]  D. Tatakis Interleukin-1 and bone metabolism: a review. , 1993, Journal of periodontology.

[106]  R. Lamont,et al.  Role of the Streptococcus gordonii SspB protein in the development of Porphyromonas gingivalis biofilms on streptococcal substrates. , 2002, Microbiology.

[107]  D. Anderson,et al.  Periodontal manifestations of the heritable Mac-1, LFA-1, deficiency syndrome. Clinical, histopathologic and molecular characteristics. , 1987, Journal of periodontology.

[108]  M. Sanz,et al.  The periodontal abscess (I). Clinical and microbiological findings. , 2000, Journal of clinical periodontology.

[109]  P. Bartold,et al.  The effect of oxygen-derived free radicals on gingival proteoglycans and hyaluronic acid. , 1984, Journal of periodontal research.

[110]  Chiara Scapoli,et al.  Modulation of clinical expression of plaque-induced gingivitis: interleukin-1 gene cluster polymorphisms. , 2005, Journal of periodontology.

[111]  A. Kantarcı,et al.  Neutrophil-mediated tissue injury in periodontal disease pathogenesis: findings from localized aggressive periodontitis. , 2003, Journal of periodontology.

[112]  Seong-Ho Choi,et al.  Distribution of periodontal pathogens in Korean aggressive periodontitis. , 2003, Journal of periodontology.

[113]  David C. Dale,et al.  Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis , 1999, Nature Genetics.

[114]  M. Soydinç,et al.  Infantile genetic agranulocytosis (Kostmann type). A case report. , 1995, Journal of periodontology.

[115]  Whasun O. Chung,et al.  Intra- and Interspecies Regulation of Gene Expression by Actinobacillus actinomycetemcomitansLuxS , 2001, Infection and Immunity.

[116]  S. Holt,et al.  Implantation of Bacteroides gingivalis in nonhuman primates initiates progression of periodontitis. , 1988, Science.

[117]  J. Gunsolley,et al.  Periodontal host modulation with antiproteinase, anti-inflammatory, and bone-sparing agents. A systematic review. , 2003, Annals of periodontology.

[118]  R. Genco,et al.  Neutrophil function and oral disease. , 1985, Journal of oral pathology.

[119]  K. Tabeta,et al.  Self‐heat shock protein 60 induces tumour necrosis factor‐α in monocyte‐derived macrophage: possible role in chronic inflammatory periodontal disease , 2002, Clinical and experimental immunology.

[120]  G. K. Johnson,et al.  Cigarette smoking and the periodontal patient. , 2004, Journal of periodontology.

[121]  L. Trombelli,et al.  Modulation of clinical expression of plaque-induced gingivitis. I. Background review and rationale. , 2004, Journal of clinical periodontology.

[122]  F. Dewhirst,et al.  Prevalent Bacterial Species and Novel Phylotypes in Advanced Noma Lesions , 2002, Journal of Clinical Microbiology.

[123]  M. Moeschberger,et al.  New Bacterial Species Associated with Chronic Periodontitis , 2003, Journal of dental research.

[124]  D. Bowden,et al.  Mutations of the cathepsin C gene are responsible for Papillon-Lefèvre syndrome , 1999, Journal of medical genetics.

[125]  F. Dewhirst,et al.  Bacterial Diversity in Human Subgingival Plaque , 2001, Journal of bacteriology.

[126]  A. Akamine,et al.  Periodontal ligament cells secrete the factor that inhibits osteoclastic differentiation and function: the factor is osteoprotegerin/osteoclastogenesis inhibitory factor. , 2001, Journal of periodontal research.

[127]  A. Schmidt,et al.  Receptor for advanced glycation end products, inflammation, and accelerated periodontal disease in diabetes: mechanisms and insights into therapeutic modalities. , 2001, Annals of periodontology.

[128]  O. Koulouri,et al.  Relative proportions of mononuclear cell types in periodontal lesions analyzed by immunohistochemistry. , 1999, Journal of clinical periodontology.

[129]  K. Havemann,et al.  Gingival crevicular fluid elastase-inhibitor complex: correlation with clinical indices and subgingival flora. , 1991, Journal of periodontal research.

[130]  G. Seymour,et al.  In situ demonstration of natural killer (NK) cells in human gingival tissue. , 1986, Journal of periodontology.

[131]  R. Lamont,et al.  LuxS-Based Signaling in Streptococcus gordonii: Autoinducer 2 Controls Carbohydrate Metabolism and Biofilm Formation with Porphyromonas gingivalis , 2003, Journal of bacteriology.

[132]  Joseph J. Zambon Guest Editorial: Actinobacillus actinomycetemcomitans in Adult Periodontitis , 1994 .

[133]  M. Sela,et al.  Superoxide formation and chemiluminescence of peripheral polymorphonuclear leukocytes in rapidly progressive periodontitis patients. , 1991, Journal of clinical periodontology.

[134]  T. Kawai,et al.  Involvement of T-lymphocytes in periodontal disease and in direct and indirect induction of bone resorption. , 2001, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[135]  J. Penninger,et al.  Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection. , 2000, The Journal of clinical investigation.

[136]  G. Seymour,et al.  Accumulation of Human Heat Shock Protein 60-Reactive T Cells in the Gingival Tissues of Periodontitis Patients , 2002, Infection and Immunity.

[137]  Emma Roberts,et al.  Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis , 1999, Nature Genetics.

[138]  W. Loesche Chemotherapy of dental plaque infections. , 1976, Oral sciences reviews.

[139]  S. Tomar Dentistry's role in tobacco control. , 2001, Journal of the American Dental Association.

[140]  G. Koch,et al.  Assessment of risk for periodontal disease. I. Risk indicators for attachment loss. , 1994, Journal of periodontology.

[141]  Makoto Umeda,et al.  Prevalence of periodontopathic bacteria in aggressive periodontitis patients in a Japanese population. , 2003, Journal of periodontology.

[142]  A. M. Ocampo,et al.  Relative proportions of T-cell subpopulations and cytokines that mediate and regulate the adaptive immune response in patients with aggressive periodontitis. , 2004, Journal of periodontology.

[143]  E. Haneke The Papillon-Lefèvre syndrome: Keratosis palmoplantaris with periodontopathy , 1979, Human Genetics.

[144]  M. Moeschberger,et al.  Association of Bacteroides forsythus and a Novel Bacteroides Phylotype with Periodontitis , 2002, Journal of Clinical Microbiology.

[145]  Michael T. Wilson,et al.  Bacterial modulins: a novel class of virulence factors which cause host tissue pathology by inducing cytokine synthesis. , 1996, Microbiological reviews.

[146]  M. Barak,et al.  Predictive Value of an Adherence Test for Acute Otitis Media , 1998, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[147]  Philip S. Stewart,et al.  Diffusion in Biofilms , 2003, Journal of bacteriology.

[148]  F. Nishimura,et al.  Periodontal disease and diabetes mellitus: the role of tumor necrosis factor-alpha in a 2-way relationship. , 2003, Journal of periodontology.

[149]  Schroeder He,et al.  Pathogenesis of inflammatory periodontal disease. A summary of current work. , 1976 .

[150]  G. Seymour,et al.  Conversion of a stable T-cell lesion to a progressive B-cell lesion in the pathogenesis of chronic inflammatory periodontal disease: an hypothesis. , 1979, Journal of clinical periodontology.

[151]  P. Kolenbrander,et al.  Effect of saliva on coaggregation of oral Actinomyces and Streptococcus species , 1984, Infection and immunity.

[152]  Thomas E. Van Dyke,et al.  Localized aggressive periodontitis is linked to human chromosome 1q25 , 2004, Human Genetics.

[153]  J. Lindhe,et al.  Conversion of stable established gingivitis in the dog into destructive periodontitis. , 1975, Archives of oral biology.

[154]  A. Roberts,et al.  Transfer of Tn916-Like Elements in Microcosm Dental Plaques , 2001, Antimicrobial Agents and Chemotherapy.

[155]  M. Newman,et al.  The predominant cultivable microbiota of the periodontal abscess. , 1979, Journal of periodontology.

[156]  S. Weiss,et al.  Neutrophil-mediated solubilization of the subendothelial matrix: oxidative and nonoxidative mechanisms of proteolysis used by normal and chronic granulomatous disease phagocytes. , 1986, Journal of immunology.

[157]  P. Kostenuik,et al.  Osteoprotegerin: a physiological and pharmacological inhibitor of bone resorption. , 2001, Current pharmaceutical design.

[158]  G. Armitage,et al.  Development of a classification system for periodontal diseases and conditions. , 1999, Annals of periodontology.

[159]  R. Gmür,et al.  Microbiological profile of early onset/aggressive periodontitis patients. , 2004, Oral microbiology and immunology.

[160]  S. Weiss Tissue destruction by neutrophils. , 1989, The New England journal of medicine.